Application of cellulose derivatives



- urethral-, ureteral and renal exploration and Patented Apr. '1, 1941 s v PIPLIolunch or onuonosnnnmv when; j riime to a micorn rsumunion cm", mm; I orporationpf ngwjgmy I: "T l t I V No D'riwinr? rin ica m emester 293 938,: 7Y1- Sefial N6.232',"i09

1 7 claims; This myention relates to compositions of tubes 0t varying shape and; length partially-orwholly composed 01.. organic derivatives, jeith'e'r' solid. or: hollow. or circular, oval, elliptical; square, rectangul'aror other cross-sectional shape,- and" in. :eneifaL-to surgical devices comprehended uh hodyfor: injection or ithdraWaIofi-iluidsE therein 4 therefrom andiormedicamentation',"or chin-- sertion-E- into: an; incision. .as :mo ts e By: me te m-x catnet rv as herein applied; is'

.dorthe'zterms exploratory and", evacuatiye; 1 5 catheters, soundsor cannulae, being When-solidi; int nded: d n i m. apa a andwhen hol lowjor insertion into a normal opening: cr me- W; understoodas comprehendingthe-van itruction ton introduction of a substanceinto the' $13 shapes-and: Iengthsoimsuaily) hollow-icon through' an openingj.. o r' the nwithdrawal 'of f lipids-E.- therei'rom, .and referred "to; under terms such as; ant'rum; colonic; elbowed; double elbQw dlcuzvet-l', eustachian, faucial; remaiem dwelling, prostntic '.ora winged catheters; t'iibesi- Heretofore;- catheter-shave been rnadevofe off the 'inaiiiphl'ato'i'; Cathetersarejoiten'nsed by H J meu ymau ',sometimes-daily; asin pr'ostatic en-p mien-tensandsnalbgous" omputations; and the" 1- initiate's'irritation; iw-hi chj'whefi continued, may 7 ops-materials Hshowinga degree: of flexibility; as i thin metal tubinm, rubber of -varying{--stages 01 yplcanization, and;compounds in ".the liquid' or 1-, liquit-Lcondition built up over a web aso fbric iusuaily byrepeateddipping-of thesame i disolution :o!=.;the;-coating: orsimpregnating mate-= v Metal:v catheters are harsh todelk'zaate" branesyprone to irritate-and wound :tissues :u'pon insertion; especially "when the tissues are i ultra jgpsitivezsandn unusually delicate, as in in-flam certain pathological :processesenanormal andlpathologioal:secretions exert asol venteflect loathe-metal which with: some metal is very-rmarkeda. '-I'heir-coniparatively lews msticitxa is also: a: disadvantage to their extensiveopplioation 'especially in :urolo'gicalfl workfia connection with: the removai 'of; same-46m; renai calculhd,

Cathetersm d ofrubberyary greatly' inelas-- jlessrdr aqiptja i m ia a a body canals,especially'the nreter wherethecanah- I v iat'ively; small and more or less tortuousand. which may be constricted 'orfeven s'ubstantially-closed by'nie'ans vor-:'momwr'mi1 r 1 other conditions present therein.

'rne na'rd 'rubber catheterswl'iile'they niay'be K of thedesired rigidityparedencintm suppleness andiplia'bility, "Ijh'e comparatively largeamounts qr s m aridu mr coinp'onnds contained there eters and does" lead to serious chronic results;

Glass-"catheters; while usuallyof smooth sora '1 race; have-a very-10w elasticity and suppleness, and"tliere-'i's'-aiways present the grave danger of 'breakage oi' chippini ofi; especially where the,

glass-fwallisfM relatively extreme thinness, as is sometimesthet case'. -Ffor thisand other reasons,' 3 the use of-"glass-cathetersinyolves an elementfot J c I danger,- and-inaddition they have a limited and a 35 'decreasing=-ran "of applicability; Y I

is; that is, catheters made {of Ena A Q faotica lly rigid with zero flexibilitm'of relativelyi' rotighfintelior due to the difliculties of imtembr g la'zfh nqivery'fragileain the thin cell I as usually-jprepared. By virtue o1" gidity-enatnel catheters are use-,

and-the roflgh interior i introdnoes ithe danger of l inomplte 'sterilization;

ticity and suppleness' dependent upon; the de'gree otvivulcanization to which the" rubber; has'alibeeniz w Wbictird, "soft"; rubhen-'oatheters=are elastic v but ;more or less porous and spon'zy. causing;diillculty in sterilization; and 're quiringesiich rigidt sterilization treatments-ms. to

materially'wshorten their period of] effectiveness? Theyalso, in. general; lack the requisiterigidity' coupled 'with the desired .flexlbility to vpenetrate ss' Oneoftheoblectsyofiny inyention is: to :overooniei-and- 'minimize the 'hereimenumerated and other idisadvantages while still conserving the points ,actdesirability"of these'instrurnents as a; class}as abplied 'to'the'various uses for which e they are norniallyjintended, and I have fcijnd that most come where e" catheter material is composed er witli' zthe"' v'ulca' iZatioh accelerators.

many-o which; arejnitrogen" m ms: en -m. their iefiectiven'ess pon'nds- 0 pm; l? v e ll ly" fin t against a.

mare; hard rubber cath *i 'ure'] an'd"w01iridldelicate often eitrem'e i f ender' to irritationsandinflam-- I 'at thie use'of thesejoath-v istf niater'iall Iiniited'; both 'asf-to scope of"; a 'p'pIication= an'd' tfo th'e techniqne' ahd experience .1-'

',: are-{used to a limited extent. 1

norms the varying contour of them 081131111110 liicli-itheyare intended to be inserted;

e 'inherentl Objections are 7 goverv en etherized'oellulds'e,especially where rthe degree of etheriflcation approaches the maximum. By etherized cellulose as, herein used, is to be understood commercially alkylated, arylated or aralkylated normal ormodifled cellulose, as

highly etherified methyl-, 'ethyl-,propyl-, butyl-, or benzyl-cellulose, or mixtures ofthe same as examples. a

For many purposes "and depending upon the physical properties desired in'the finished oath eter, and its size, dimensions, wall thickness, etc.,

l the. desired elasticity, suppleness,iiexibility, stability, and freedom from objectionable features} for the purposes for which it' is intended, If'may use a single or a mixed celiulose'etherfor"-mix ture of cellulose ethers, andwherejadditional suppleness, elasticity, etc., is desired, suitable plasticizers, ilexilizers, softeners, @extensiilers' or. suppleness-inducing components may be incorporated with theceliuloseether in amount and. of nature to impart the kindand degree of characteristicsdesired. The highly etherifled ethylcelluloses and benzylecelluloses'fhave been iound especiallyuseful in thislconnection, on account of the number and 'amountof suitable plastiiying components whichv may be harmoniously in-g corporated therewith to inducethe specific propthe extent of I the same1'de A erties required and sired.

The cellulose ethers, H1555, are insoluble in, and not detrimentally aflected by ptyalin,

pepsin, trypsin, oleopsin, steapsingand other body enzymes and fluids, theproducts elaborated sible, with the production of a cellulose ether substantially insoluble in water. In the use of dissimilar radical etherified celluloses as herein comprehended, in general it has been found that the porosity of the plasticized and extruded material is less and the solubility in normal and pathological body fluids lower, where the higher molecular weight radical preponderates in comparison to the. lower molecularweight radical. That is, assuming cellulose in its simplest form as admitting of a tri-derivative being formed and that ethyl and benzyl are the two groups to be combined therewith, then better results have been .fo'btainedbyme by'the use of a monoethyl-dibenzylcellulose,for example, than with a diethylmonobenzylcellulose, or product approximating -ingcr'imposition thereto; Similarly, if an ethylpropylcellulose is to be employed for catheter formatipn according to this invention, I prefer to make use of a product which more nearly approximatesv a monoethykdipropylcellulose, than such as ethylbenzylcellulose, are not of maximum commercial degree of. etheriiication. They are in the gall bladder, liver, and kidney, both those that are normal to the healthy'body'andthose.

formed under pathological conditions; they canbe producedof a high degree. of flexibility, are not adversely affected by the usual anti septics, disinfectants, bactericides', vboth those of V metallic and nonmetallic origin. usually applied for sterilization purposes.

As iswell known, many of pathological body secretions either are distinctetherifledenough to;meet most of the technical requirements for which. they are intended, butin order to prepare a mixed etherifled cellulose the processbecomesmore costlyand this-expense is not Justified. by the usual requirements for cel- '7 lulose ethers in the lacquer and plastics arts.

1y acid in reaction as the hydrochloric ,acidiilx' the gastric juice, the bile acids,-uric acid and, the like," while other secretions are "of pronounced" These chemically reactivev bodies often aided by, enzymic action, exert, an

alkaline reaction.

appreciable dissolvingand decomposing effect especiallywhere in some instances, the tubular surgical device is left'in the body for an extended period as often is the case' in drainage treat-'- ments. With the simple celluloseestersj as the nitrate or the acetate, a saiion'ifying action re-' sults, whereby a decomposition of thefcellulose ester takes place by a splittingofl of acid radical;

Asthe culmination of a series of quantita tive researches, the surprising andunobvious, observations has been-made, thatcelluioseethers', .and specifically the dissimilar or'mixedetherifled celluloses as alkyl aralkylcellulosesof comparatively high degree of etheriflcation are sub- I It is generally recognized that the water-in- 2 solubility. swelling-resistance in'the presence of water or other hydrous substances, and innocuousnesstoehemicalreagents, all gradually in-- crease. in direct relation to the proportion of j' ether substituents in the cellulose aggregate. but

- heretofore no quantitative work has been done in upon a cathet'er or instrument of analogous use,-

' when made of rubber or a simple cellulose ester,

determining the relativeinsolubility and innocuousness innormal and pathological-fluids of alkylaralkylated celluloses approachingthe theoretical maximumin degree of etheriiication. In using an instrument of the catheter type, and in drain-' age after operations, especially in the treatment of renal calculi and in renal surgery, often itbecomes necessary to allow the instrument to restantially insoluble in and unaffected by'chem'i cal andother components elaborated by 01 in the human body in health and disease. a

This has been found tohold to the maximum degree when ethylbenzylcellulo'se or ethylpropylcellulose is the etherifiecl cellulose employed, and where the etheriiication has been allowed to proceed .to commercially maximum etherification, that is to say, where etherification of the cellulose has resulted in the introduction of ethylbehzyl, ethylpropyl,"etc., rests to the extent of-% to of theoretically posmain partially within the body for several days in contact with highly' sensitive membranes. Under such circumstances, it becomes of prime 7 importance to have a catheter which will undergo substantially no swelling while in contact with the normal and pathological body fluidswhich may hem and around-it, r

ause. of the, intumescing .action of. theiacidand alkaline body contents on the usual; and commercial mixed cellulose ethers, they are unsuitable for the purpose intended-in this invention. Where,"- heretofore, the mixed cellulose ethers have been found unsatisfactory in 7 this field due tothe limitation above outlined, I have overcome; these difiiculties by either ether ifying cellulose with a theoretical excess of mixed" etherifying agents under optimum conditions, or by I further etherifying a cellulose ether"with-=-a dissimilar .etherifying' agent,. such that the final, etherifiedcellulose has been etheritled to substan tially the maximum.

Another discovery made by me is that in we: Y

where the amounts of etherifying and solubilizing s catheter substance so that the softening point of the completed catheter or surgical instrument, if desired, may be reduced to about the normal temperature of the human body. Thus the rigidity of the instrument may be modified by insertion in the body. In this way, these catheters are suits le for exploratory work, especially in connection with renal treatment and examinations, a usage which would be difiicult if not impossible with a rigid and non-thermoplastic body (as rubber).

The cellulose ethers of dissimilar radicals, as a body are characterized by relatively great stability and apathy to reaction with chemical reagents, while still conserving an unusually high degree of inherent flexibility. The cellulose ethers may be treated with lye solutions of high concentration with impunity, since there is no acid radical to saponify off by alkaline treatment as is the case with the simple cellulose esters, and

in addition are inert to many chemicals which injuriously affect rubber and other materials of which catheters of the present art are made. It

is impossible to increase the elasticity of rubber at will by the addition of products thereto, whereas with the cellulose ethers, by selection of the appropriate plastifying agent or combination of the same, and the ratio between plastifier and cellulose ether, there is a very wide range of flex- "and usually comprises an outer end or end held by the operator, which may be of the same exterior diameter as the remainder of the tube portionor may be flared or otherwise enlarged; the opposite end called the tip or beak, being that end intended for insertion, and which may be of the same diameter as the tube portion, or may,

be smaller, and is usually made in many shapes and in a variety of ways. The tip may be a portion of the original tube with one or more orifices therein, or it may be a separate piece immovably attached to the body of the catheter ibility and' elasticity possible, which peculiarly adapts the cellulose ethers for use in the catheter industry. Phenols, iodides and other halogen inorganic or organic compound of normal bactericidal concentration areinert in unfavorable action to thecellulose ethers of degree of etherification comprehended herein.

The antiseptic, local anesthetic, fungicide, bactericide, medicament, or other addition of therapeutic value to the catheter substance may be incorporated'therewith in any approved manner, such, for instance, as dissolving the same in a relatively small amount of harmonious solvent or solvent combination, incorporating the same with the etherized cellulose in any approved manner as by malaxation, then preferably removing the volatile portion by an evaporative step before extrusion, so that the medicament is uniformly disseminated throughout the etherized cellulose mass.

The'etherized celluloses as a class are pecutube -by means of an agglutinant, by fusion, or in any other manner. The shape, configuration, length, and number of orifices therein, may vary considerably, depending upon the specific use to which the instrument is to be applied.

Having determined the degree of ether prop- I erties intended from the desired use for which the instrument is designed, the kind'and nature of mixed cellulose ether is selected, the amount and kind of thermoplasticizing body added if any be used, and the composition by means of solvents, non-solvents and solvent and'non-solvent combinations, gelatinized or colloided to the degree required, then extruded through an orifice of appropriate size and shape, into tubular or other form.

. In general, it has been found the melting point is raised and the deleterious action of water on the mixed cellulose ether decreases with the number of dissimilar radicals in the etherized cellulose, and increase in molecular weight of the same. For the aboveand other reasons, I have composition, to increase the hardness, lessen the liarly adapted for use in this connection by virtue of the fact that they may be extruded in practically non-porous'condition, may be dyed, pigmented, or otherwise treated without detrimentally affecting their normal stability or usefulness; and'the elasticity, being inherent in the cellulose ether body, persists unchanged for an indefinite period of time. Therefore, a widely varying degree of desirable properties may be obtained, especially as to elasticity, plasticity, suppleness and flexibility of the ether, and these inherent desirable properties may be considerably enhanced by the addition to the cellulose ethers of suitable plasticizing bodies now known to the cellulose ether art, such as aliphatic and carbocyclic esters of lactic, glycollic, tartaric, phthalic and other acids, aryl phosphates, cyclohexanol esters, synthetic resinous bodies such as the halogenated diphenyls, the substituted sulfonamides, and the like.

A catheter, in general, may be considered as a tube, straight, curved, elbowed, 'etc., depending upon the use for which it is normally intended,

degree of permeability or for other reasons, after which the tube portion is expanded or the diameter otherwise modifiediat the outer end,'and the tip or beak portion may be punched, drilled, or otherwise one or mor orifices placed therein after closing the beak end,-as with a cellulose ether composition, or'a separate tip may be made and coapted onto the tube portion by means of an adhesive, by heat, by heat and pressure, or in any other way,said tip being of the size and nature required for the specific purpose intended. The number, size, spacing and location of orifices in the beak portion maybe modified at will.

The cellulose ether composition maybe colored, with dye or pigment or both, to render the instrument distinctive upon'observation; it may be printed or lithographed upon, either under or on the final exterior coat if the extruded member is subjected to a dipping process after extrusion, or various antiseptics, remedial agents, analgesics or local anesthetics may be incorporated in the cellulose ether plastic mass to induce a. therapeutic effect on the organs with which the oatheter may normally be brought into contact. Urethral and especially ureteral catheter explorations are usually relatively painful operationsso that the incorporation within the catheter mass of local anesthetics,

analgesics and the like, is often indicated.

for urological ,work as with urethral and ureteral catheters, the cellulose ether may have incorpo- .and other salts "or mixtures of salts suitable for this purpose. As an example, given for illustrative purposes only, I have found an excellent composition for this purpose to be composed of 100 parts cellulose ether plastic mass to about 100 to 150 parts lead sulfate, although these propor-' tlons may be varied, from the amounts above stated, depending upon the cellulose ether composition, the dimensions and thickness of the catheter tube, the nature of the opacity-inducing'body used, and the particular roentgenological diagnosis to be made.

Urethral catheters are usually flared on the outer end, substantially round, of exterior diameter 0.06 to 0.25 inch, interior diameter sufliciently large usually to admit a ureteral catheter. Ureteral catheters are usually not flared on the outer end, and vary in tube diameter from 0.04 to 0.10 inch external and about 0.015 inch internal diameters. For colonic work, a round tip is usually used, the exterior diameter being up to 0.75 inch diameter. An antrum catheter usually has an exterior diameter range of 0.075 to 0.15 inch and a varying internal diameter. The exterior and interior diameters will, of course, be adjusted by the extrusion operation, taking into the consideration the amount, if any, oi volatile solvent present and the relative volatility of the plasticizing portion added to the mixed cellulose ether prior to the extrusion operation. The shape of the catheter tip may vary considerably, as in the olive, round or whistle tips, as examples.

In general, the substantially maximum alkylaralkylated celluloses have a relatively high inherent thermoplastlcityfwhich property may be considerably augmented and varied in degree by the incorporation therewith of suitable known cellulose ether plasticizers and flexibility-inducing compounds, and still conserve the relatively high and permanent stability to, and insolubility in chemical reagents which characterize the cellulose ethers in general. Likewise, it has beenfound that by the use of certain cellulose ether pla'sticizing and thermoplasticizing agents, the stability of the etherized cellulose may be augmented, the porosity diminished, and the suppleness and flexibility materially increased, without concomitantly decreasing otherwise valuable inherent characteristics.

There has been described a method of producing a catheter by first forming a textile core, dipping the core into a solution of cellulose or other compound, drying the same, then repeating the process until there has been built up on the textile center orcore a sufficient thickness of layers for the purposes intended. However, such constructed tubes are porous, they have pinholes and blisters therein which increase the natural porosity, as compared with the cellulose ether composition of the nature as herein set forth which lead sulfates and lead salts, barium has been compacted by necessarilyhigh pressure involved in the extrusion operation to a unitary non-porous whole, and is composed of a unitary material throughout its substance. With a fabric core catheter built up in manner as above indicated, there is tendency upon use for the textile core to become frayed, and a fragment may be broken off and remain in the bladder or kidney, thus providing a. nucleus or nidus around which a calculus may form.

Therefore, the catheter involved in this invention is of homogeneous structure throu hout, and there is no dissimilar material core which may break off, fray or cause an impediment in R-ra! work or similar investigation, on account of variation of opacity.

At the close of the extrusion operation, the catheter may be dipped, sprayed, or otherwise coated with a cellulose compound in solution, and the instrument may be smoothed, polished, print ed upon or otherwise treated to produce a finished appearing instrument. The printing operation may be conducted upon the extruded cellulose compound, either before or after the catheter is coated with a fluid compound, and either before or after the polishing or other finishing operation.

What I claim is:

'l. A tubular surgical device comprising a water-insoluble etherized cellulose containing dissimilar rests and of maximum degree of etheriiication.

2. A tubular surgical device comprising a waterinsoluble alkyl-aralkylated cellulose of maximum alkyl-aralkylation.

3. A flexible, tubular surgical device of homogeneous structure, said device comprising a thermoplastic alkyl-aralkylated cellulose of substantially maximum degree of alkyl-aralkylation.

4. An instrument for withdrawal of fluids from the body comprising a water-insoluble alkylaralkylated cellulose of substantially maximum alkyl-aralkylation,

' 5. A catheter comprising a substantially wholly ethyl-benzylaiged ethylbenzyl-cellulose containing plasticizer. 1,

6. A smooth,'wa ter-insoluble catheter comprising an ethyla'ted-benzylated cellulose of commercially maximum degree of alkyl-aralkylation in which the benzyl predominates.

7. A catheter comprising a relatively long, hollow tube of small-external diameter formed by extrusion from a thrmoplastic mass of alkylaralkylated cellulose so as to be externally smooth, continuous, non-porous and highly flexible but having sufiicient inherent tensile strength and longitudinal rigidity to permit insertion by itself into and through long, narrow and tortuous bodily passages, the degree of alkylearalkylation of said mass being so high as to render said catheter water-insoluble and unaffected by moisture, substantially inert -to bodily ams and medicaments and to have the othe inherent characteristics aforesaid.

VINCENT JEROME FLYNN. 

